The invention relates to liquid chromatography detectors and more particularly to an acoustic method for measuring the concentration of a material in a liquid chromatography effluent by measuring changes in ultrasonic attenuation.
Liquid chromatography is a separation technique in which a liquid moving phase, the effluent, is passed through a solid or a liquid stationary phase. As the mobile phase containing a mixture of compounds passes down a separation column, various compounds in the mobile phase are separated because of the difference in retention of each compound by the stationary phase. The effluent liquid thus contains a series of zones or slugs of separated compounds. Liquid chromatography is a particularly valuable technique because it is useful for large molecular weight, biochemical and/or organic mixtures and for thermally unstable and nonvolatile compounds. A liquid chromatography detector must measure the concentration of a solute in a liquid chromatography effluent. The detector must have response characteristics to measure the concentrations of the different compounds as the effluent flows through.
In the most common application of liquid chromatography separation techniques, it is desired to separate out known compounds and measure their concentrations. This procedure is critical to quality control in manufacturing processes, such as the production of drugs. It is also possible though somewhat more difficult to separate out unknown compounds for the purpose of identification of the compounds as well as obtaining a measurement of the concentration of the compound.
There are two basic detection systems presently in use for liquid chromatography. The ultraviolet detector, which measures UV absorption, is most frequently used because of its high sensitivity. However, since the ultraviolet detector relies on the presence of a strong UV absorption band within the wavelength range of the detector, it is not a universal detector and cannot be applied to all compounds of interest. Furthermore, even when the compound exhibits a suitable UV absorption band, absorption from the solvent may prevent reliable measurements at low concentrations. The refractive index detector, which measures changes in the optical refractive index, is the second most widely used detector and may be useful where a suitable UV absorption band is not present in a compound. Although the refractive index detector is a more universal sensor, its sensitivity is quite low since the optical refractive index differs by less than a factor of two for almost all liquids of interest.
Other detectors are used in more specialized and limited applications. The moving wire or transport detector produces a solute residue which is pyrolyzed. Other detectors are based on fluorescence, scintillation, heat of adsorption, infrared absorbance, electrical conductivity, capacitance, and polarography.
There is a need for a detector that is more universal than the ultraviolet detector and at the same time more sensitive than the refractive index detector. A detector is required which measures a universal physical parameter of liquids that has a wide range of values so that all liquids can be measured with the same apparatus with a sensitivity as good or better than that of the ultraviolet detector. However, unlike the situation in gases, there are few readily measurable parameters of liquids that possess a wide range of values. Most liquids have roughly similar densities, thermal properties, and refractive indices, making these parameters unsuitable for high-sensitivity detection schemes.
Accordingly, it is an object of the invention to provide a universal liquid chromatography detector with high sensitivity.
It is also an object of the invention to provide a method and apparatus for liquid chromatography detection which measures a universal physical parameter of liquids that has a wide range of values.
It is a further object of the invention to provide a universal method and apparatus to measure the concentration of a solute in a solvent.
It is another object of the invention to provide a method and apparatus for measuring ultrasonic attenuation in liquids with high sensitivity.